Physiologic multivalvular regurgitation during pregnancy: a longitudinal Doppler echocardiographic study

International Journal of Cardiology, 40 (1993) 265-212 0 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved. 0167-5273/93/%06.00

265

physiologic ~ultivalvular regurgitation during pregnancy: a longitudinal Doppler echocardiographic study* Orlando Camposa, Jose L. Andradea, Jose Bocanegraa, John A. Ambroseb, Antonio C. Carvalhoa, Keiko Harada” and Eulogio E. Martineza ‘Division of Cardiologv, Es&a

Paulista de Medic&a, Sao Paulo, Brazil and ‘Division of Cardiology. Mount Sinai School New York, USA

of Medicine,

(Received 19 October 1992; revision accepted 24 March 1993)

Valvular function, assessed by Doppler technique, has not been extensively investigated during normal pregnancy. To prospectively study this feature, 18 normal pregnant women were followed during their pregnancies and pue~rium, with serial clinical and pulsed-continuous Doppler ~h~ardiographic examinations. In four gestational periods and the pue~rium, we analysed: (a) ventricular and atria1 dimensions, as well as valve annular diameters; (b) prevalence and characteristics of trivial valvular regurgitations. During pregnancy, slight but significant increases of the four cardiac chamber dimensions and valve annular diameters were observed, except for the aortic ring. The prevalence of physiologic valvular regurgitation in early pregnancy (mitral, 0%; tricuspid, 38.9%; pulmonary, 22.2%; aortic, O%), was similar to a control group of 18 healthy non-pregnant women. As pregnancy evolved, there was a progressive and significant increase of multivalvular regurgitation, maximal at full-term (mitral, 27.8%; tricuspid, 94.4%; pulmonary, 94.4%, P < 0.05vs.early pregnancy). Aortic regur~tation was not detected in any stage of pregnancy. In the puerperium, mitral regurgitation resolved, but tricuspid and pulmonary re~r~tation were still significantly prevalent (83.3% and 66.7O/, respectively, P < 0.05vs.early pregnancy). It is concluded that physiologic multivalvular regurgitation is frequent in pregnancy, mainly involving right-sided valves in late gestational periods, occasionally persisting in the early puerperium. Chamber enlargement, valve annular dilatation, and increased prevalence of trivial valve regurgitation are time-related events during normal pregnancy, resulting from a reversible cardiac remodeling process induced by physiologic volume overload. These aspects should be considered for a correct interpretation of Doppler ~h~ardio~aphic findings in pregnant women with suspected heart disease. Key words: Pregnancy; Doppler echocardiography;

IIltdUCtiOO

Normal pregnancy is characterized by increases in total blood volume and cardiac output Cl]. Correspondence to: Orlando Campos,Rua MadreCabrini332, Sao Paulo, SP-CEP 04020, Brazil. *Partial data have been presented at the Annual Meeting of the American College of Cardiology, 1990, see Ref. 3.

Valve insufficiency

These physiological adjustments must be taken into account in the cardiologic assessment of pregnant women. In this setting, Doppler echocardiography has been a useful tool without risk for the evaluation of suspected organic lesions, especially when cardiac murmurs are detected during pregnancy. Despite its current clinical use, little is known about valve function assessed by Doppler techniques in normal pregnancy.

266

Tricuspid regurgitation, detected by pulsed Doppler, has been reported to occur in normal pregnant women with new functional systolic mu~urs, as a physiological event [Z]. However, the prevalence of this finding, as well as its time course during normal pregnancy has not yet been described. Moreover, there are no data concerning regurgitation in the other cardiac valves of normal pregnant women. The present study was prospective and longitudinal, designed to evaluate the normal pattern of transvalvular flow of the four cardiac valves with Doppler technique in a group of normal pregnant women, without known cardiac disease. Our main purpose was to investigate the occurrence and behavior of physiologic valvular regurgitation in the evolution of normal. pregnancy.

Groups Study group From May 1988 to April 1989, in the outpatient clinic of the Cardiology Division of Escola Paulista de Medicina, 18 normal pregnant women (age 14-35 years, mean 23 f 5) were prospectively examined for the duration of their pregnancies. All subjects gave informed consent for their voluntary participation. The study protocol was approved by the ethical committee of our institution. Cardiovascular history, physical examination, blood and urine analysis, and 12lead electrocardiogram at rest were normal in all subjects during the investigation. An initial echocardiogram was performed to exclude any cardiac structural abnormality that could be missed in the initial clinical evaluation. Subsequently, all pregnant women underwent full M-mode, two-dimensional echocardiographic and Doppler examinations. Complete evaluation was repeated for all subjects at consecutive, pre-determined time intervals, comprising four gestational periods: 8th to 14th week (Tl), 20th to 24th week (T2), 30th to 34th week (T3), 36th to 40th week (T4), and one puerperium period involving the 3rd to 6th week postpartum (T5). Of the 18 women, 15 were nulliparous and all subjects had single, full-term, uneventful pregnancies resulting in deliveries of live newborns.

Control group Eighteen healthy age-matched non-pregnant women with comparable pregestational body surface area were selected, and were sub~tted to a single clinical and Doppler echocardiographic evaluation, similar to the study group. All control subjects were nulliparous, non-smokers, nonathletic, and not using oral contraceptives. Doppler rne~~n~

echocardiograpbic

technique

and

Instrumentation and technical procedures Image acquisition and pulsed Doppler examination were performed by means of a comercially available duplex pulsed Doppler machine (ATL MK 600), equipped with a 3.0-MHz mechanical transducer. Continuous Doppler examinations were made with an SC 6300 Sonocolor continuous Doppler instrument using a 2.5-MHz Pedoff transducer. Pulsed and continuous Doppler spectral curves, as well as M-mode echocardiograms were registered by a strip-chart printer at a paper speed of 50 nuns along with the eletrocardiogram. All studies were video-recorded for further analysis. Subjects were examined in left lateral decubitus position. After a IO-min resting period, a comprehensive Doppler echocardiographic study was made, comprising M-mode measurements, twodimensional evaluation, and a full examination of the four cardiac valves by pulsed and continuous Doppler techniques. All Doppler echocardiographi~ examinations of pregnant and control were performed by the same investigator. Recorded data were blindly analysed by two independent observers. Quantitative measurements were determined by mean values obtained from both observers (inter-observer variability less than 12%). The following data were analysed. (a) Crabber Dimensions. Left atrium and left ventricle diameters were obtained with standardized M-mode measurements 141.Right atria1 length and right ventricular width were obtained by twodimensional images, assessed from the apical fourchamber view at end-systole and end-diastole, respectively [S]. (b) Valve annular diameters. Mitral and tricuspid annular diameters were measured from

267

the apical four-chamber view [5] at end diastole. Aortic and pulmonary annuli were measured in parasternal long axis and short-axis views respectively [5], at mid-systole. Chamber and annular dimensions resulted from average values of three to five consecutive beats during normal expiration. (c) Evaluation of valvular regurgitation. Spectral curves of transvalvular blood flow velocities were obtained by means of a systematic examination of the four cardiac valves on each cross-section by pulsed Doppler, and complemented by continuous Doppler technique, using parasternal and apical approach. Valvular regurgitation was characterized when abnormal, turbulent, high-velocity signals from the pulsed Doppler spectral display were found emerging from the leaflets coaptation plane during systole for atrioventricular valves, and diastole for semilunar valves [6,7]. Regurgitation should occupy at least half of systole or diastole [8], and should last longer than 100 ms after valve closure [17]. Once regurgitation was detected, it was graded semiquantitatively according the depth of the regurgitant signal into the receiving chamber (atria1 cavity for atrioventricular valves and ventricular outflow tract for semilunar valves) and estimating its relative size in orthogonal views [6-81. Continuous Doppler examination was further performed to confirm the presence of the regurtitant jet, and to measure its maximal velocity. A ‘true’ valvular regurgitation was considered only when unequivocal signals were found in both Doppler techniques in at least five consecutive cycles, and established independently by consensus of the two observers. Any difference of opinion was settled by revaluation of the records together.

TABLE 1 Demographic and clinical data from women in early pregnancy compared to control. Data

Age (years) Multiparous Weight (kg) Height (m) Blood pressure Systolic’(mmHg) Diastolic(mmHg) Heart rate (beatsimin)

Pregnant women at Tl (n = 18) 23

+z 5 308 54.7 f 8.1 1.55 zt 0.06 Ill f 10 70 f 6 69 f 4

Control group (n = 18)

22

P-value

f 5 0118 55.3 zt 6.2 1.56 f 0.05

NS NS NS NS

118 f 13 72 zt 5 71 zt 12

NS NS NS

Tl period, 8th to 14th week of pregnancy; NS, not significant (P > 0.05). Values expressed by mean f 1 standard deviation, except for multiparity.

pregnant women in periods Tl-T5. The chisquare test was used to compare the prevalence of valvular regurgitation of pregnant women at period Tl, to the control group. A P-value C 0.05 was considered to be significant. Results Some demographic and clinical characteristics of the study group and control subjects are summarized in Table 1. There were no differences between early pregnancy (Tl) subjects and control group. Valvular regurgitation prevalence

Statistical analysis The unpaired Student’s t-test was used to compare demographic and clinical data from the pregnant women at period Tl and control group. Analysis of variance was used to compare chamber and annular dimensions from pregnant women in periods Tl to T5. The unpaired Student’s t-test was used to analyse differences of the same variables between period Tl of pregnancy and the control group. The Cochran test was used to compare the prevalence of regurgitation in each valve of

The absolute and relative frequencies of valvular regurgitation for each valve, and its temporal evolution during pregnancy (Tl-T4) and puerperium (T5) are demonstrated in Fig. 1. The occurrence of valvular regurgitation at the beginning of pregnancy (Tl) was limited to right-sided valves (tricuspid, 38.9%; pulmonic, 22.2%). A similar incidence was found in the control group (tricuspid, 44.4%; pulmonic, 38.9%; P-value NS vs. Tl). As pregnancy progressed, the incidence of tricuspid and pulmonary regurgitation increased

268

1 80% 80%

Tl

T2

T3

T4

control

Fig. 1. Prevalence of physiologic valvular regurgitation during pregnancy (Tl to T4, see text for details) and puerperium (T5), according to each valve affected. *P < 0.05 vs. Tl.

significantly from baseline (Tl), to 83.3% and 61.1% respectively at T2 (P < 0.05 vs. Tl), to 88.9% and 88.9% respectively at T3 (P < 0.05 vs. Tl), and to 94.4% and 94.4% respectively at T4 (P < 0.05 vs. Tl). Although declining in the puerperium (T5), tricuspid and pulmonary regurgitation frequencies (83.3% and 66.7%, respectively), were significantly higher than early pregnancy values (P < 0.05 vs Tl). Mitral regurgitation occurred in a lower incidence than right-sided valvular regurgitation. At baseline (Tl), no subject had mitral regurgitation. At T2 and T3, the incidence increased to 11.1%. At T4, the incidence increased significantly to 27.8% (P < 0.05 vs. Tl), resolving in the puerperium (T5). Aortic regurgitation was not identified in any stage of pregnancy in this group, nor it was in the control subjects. Valve regurgitation characteristics In all stages of pregnancy and the puerperium, valve regurgitation assessed by pulsed Doppler was detected only near the valve leaflets, emerging from the coaptation site. The maximal distance of the mitral regurgitant signal was no farther than 1.0 cm from the mitral valve plane. Tricuspid regurgitation was detected at a maximal distance of 1.5 cm from the valve leaflets, except in two pregnant women at term (T4), whose regurgitant

signal was 2.0 cm distant from the tricuspid valve. The pulmonary regurgitant signal was observed at a maximal distance of 1.5 cm only in three instances, corresponding to three pregnant women at term (T4). In the remaining instances, the distance did not exceed 1.Ocm from the valve leaflets. Right-sided valve regurgitation of pregnant women, assessed by continuous Doppler, exhibited spectral curves with relative low amplitude regurgitant signals with decreasing velocities. Peak velocities of tricuspid regurgitant jet varied from 1.7 to 2.2 m/s, with pan-systolic signals. Pulmonary regurgitation produced peak velocities ranging from 0.9 to 1.5 m/s, with mid-late or holodiastolic signals. The regurgitant signals became stronger during the final stages of pregnancy, depicting well-defined spectral envelopes. Mitral regurgitation produced the weakest regurgitant signals, with poorly defined spectral curves occupying early-to-mid or holosystole. Peak velocities from mitral regurgitant jets, although higher than 2.0 m/s, were difficult to identify, and, for this reason, were not reported. The control group exhibited similar patterns of right-sided valve regurgitation to the study group, Chamber dimension and annular diameter Chamber and annular measurements during pregnancy and puerperium are listed in Table 2, in comparison to measurements from the control group. Early pregnancy (Tl) measurements of cardiac chambers did not differ from control values, except for left atria1 diameter, which was slightly but significantly larger among pregnant women. There was a mild, but significant increase in the dimension of all cardiac chambers during pregnancy. A more marked and progressive dilatation could be demonstrated for right-sided chambers, which peaked at term (T4), representing a mean increase of 19% (right atrium), and 18% (right ventricle) above the initial period (Tl). The left-sided chamber enlargement, although gradual, was only significant with respect to early pregnancy (Tl). It was less pronounced than right-sided chamber dilatation at final periods of pregnancy, representing on average, an increase of 12% (left atrium) and 6% (left ventricle) above Tl values. In the

269 TABLE

2

Evolution

of chamber

Dimension

dimension Pregnant

and valve annular

during

pregnancy

and puerperium

compared

to control

women

TI Chamber dimension LV (mm) LA (mm) RV (mm) RA (mm) Annular diameter Mi (mm) Tr (mm) Pu (mm) Ao (mm)

diameter

group

Control T2

T4

T3

TS

41.4 29.6 30.1 42.8

f 3.1 zk 2.1 f 2.0 f 2.3

42.1 31.5 31.9 47.4

f zt f f

2.2* 2.4* 2.1 2.4*

43.0 33.1 35.5 50.8

f zt f f

1.7; 2.4% 3.2*# 2.7*#

43.6 32.8 35.5 50.9

f f zt f

2.5* 3.0* 2.3*# 2.8*#

41.8 f I.8 29.9 f 3.1 31.1 l 2.1 46.6 f 3.3*

40.1 f 3.0 27.9 + 2.4+ 28.5 f 3.0 43.7 l 4.4

22.5 22.1 19.6 18.1

f * zt zt

22.8 23.1 22.1 17.5

f f f zt

0.9 1.0 I.71 0.8

23.8 24.7 23.9 18.0

f f f f

I.l*# 1.3*# l.5*# 0.7

24.0 24.6 25.3 18.2

f f f zt

1.2*# l.l*# 2.3*# 0.6

22.5 22.3 22.9 18.3

20.0 20.0 20.8 17.8

I.5 I.7 1.8 0.9

Tl to T4: periods of pregnancy; T5: puerperium (see text for details); LV: left ventricle; right atrium; Mi: mitral; Tr: tricuspid; Pu: pulmonary; Ao: aortic. *Values > Tl, P < 0.05. #Values < T2, P < 0.05. +Values < Tl. P < 0.05.

puerperium (T5), chamber dimension declined to initial values, except for the right atrium, which was still significantly enlarged compared to Tl , when measured 3-6 weeks (mean 5.2 weeks) postpartum. Similar findings were noted with pulmonary, tricuspid and mitral valve annular diameters, which exhibited gradual and significant enlargements, mainly in later periods of pregnancy when compared to Tl (28%, 14% and 8% of mean increase, respectively). These annular enlargements resolved post-partum, except for the pulmonic valve annulus. Aortic annular diameter did not vary significantly at any stage of pregnancy or in the puerperium. Discussion Prevalence and characteristics of physiologic multivalvular regurgitation during pregnancy and the pueqerium Our study demonstrated a progressive increase in the prevalence of physiologic tricuspid and pulmonary regurgitation, as well as the transient development of trivial mitral regurgitation during pregnancy. These observations not only confirmed the finding of tricuspid regurgitation during nor-

+ f f f

I.0 1.3 2.l* 0.7

LA: left atrium:

f 1.4+ f 1.5+ f 2.1 f I.1

RV: right ventricle;

RA:

ma1 pregnancy, as first described by Limacher et al. [2], but also characterized the occurrence of multivalvular involvement by physiologic regurgitation induced by pregnancy. The existence of trivial or mild valvular regurgitation, assessed by Doppler techniques in structurally normal hearts of non-pregnant individuals is well established [6-211. Because of the influence of many technical and biological factors over physiological valve regurgitation, there is a wide spectrum of normal flow patterns in different subsets of individuals, that must be recognized. It is known that the prevalence of this physiologic finding varies according to differences in methods of investigation, instruments settings, or criteria for physiologic valve regurgitation [ 17,19-201, besides age [6,7,18], gender [8,11], body habitus [ 14,171 and physical conditioning [ 19-211. Pregnancy, as observed in our study, must be considered as another factor which may affect the behavior of physiologic valve regurgitation of young women. The characteristics of valvular regurgitation assessed by Doppler in the pregnant women of our study were similar to the control group, representing trivial or mild degrees of valvular reflux. Comparable patterns were described in other reported series with non-pregnant subjects, with respect to the extension [6,8,17-201, or

270

to the peak velocities of the regurgitant signals [8,1 l] in normal valves. Stronger regurgitant signals from cardiac valves observed by us in late periods of pregnancy (T3, T4) suggest increased regurgitant volumes [22]. Despite high pressure differences in left-sided chambers, we were not able to register a well defined, high-amplitude spectral curve of mitral regurgitation during pregnancy, as observed in non-pregnant individuals [7], probably reflecting small regurgitant volumes. Chamber and annular dimensions during pregnancy and its relationship to physiologic multivalvular regurgitation The influence of transient volume overload of normal pregnancy on cardiac chambers enlargement has been previously documented by echocardiographic studies [23,24], and was confirmed in our study. We observed a global and gradual dilatation of the four cardiac chambers during normal pregnancy, slightly more evident for the right atrium and right ventricle. In addition, we found a progressive increase in valve annular diameters throughout pregnancy, except for the aortic annulus. These findings are in accordance with previous publications regarding tricuspid [2,25], mitral and pulmonary [25], and aortic [24,26] annuli size during pregnancy. The increase in the prevalence of valve regurgitation seen in our study could be due to relative enlargements in respective valve annuli, consequent to cardiac chamber dilatation, as pregnancy evolved [2]. This reversible cardiac remodeling process results from transient hypervolemia and increased venous return during normal pregnancy [23,24], rather than the hemodynamic effect of multivalvular regurgitation. Annular dilatation, with subsequent partial and ineffective leaflet coaptation, probably represents the main determinant of pregnancyinduced transient valvular incompetence [2], with some particularities according to each valve involved. Residual dilatation of some cardiac chambers and valve annuli after delivery may be responsible for the high prevalence of tricuspid and pulmonary regurgitation, persisting until the recent puerperium. Perhaps the total resolution of this cardiac adjustment process induced by preg-

nancy, demands a longer time to return to baseline conditions before conception [25]. Predominance of physiologic right-sided valvular regurgitation during pregnancy Our findings indicate that the increased prevalence of physiologic valvular regurgitation during pregnancy was more evident for tricuspid and pulmonic valves, which were regurgitant in almost all pregnant women at term. Right-sided valvular regurgitation predominated in many series of young non-pregnant normal subjects [6- 14,171, and well-conditioned or athletic women [ 19-2 11. Proximity of right-sided heart valves to the transducer may increase the ability to detect regurgitant signals, and has been evoked to justify these findings [8,14,17,20]. Probably, some anatomic characteristics of right-sided cardiac structures may account, in part, for these differences in valve function during pregnancy. Rightsided valves have thinner leaflets with less fibrous and more compliant annuli than left-sided valves [27,28], therefore more susceptible to valve incompetence by annular dilatation when submitted to the hemodynamic burden of pregnancy. On the contrary, a more dense, non-distensible fibrous texture, could avoid or minimize aortic annuli dilatation in pregnancy, preventing aortic regurgitation. It is possible that similar functional mechanisms may be present in other types of cardiac adjustments to physiologic loads, associated with increased prevalence of multivalvular regurgitation, like continuous physical exercise in non-pregnant women [19-211. Study limitations The use of conventional pulsed and continuous Doppler without color flow mapping, may represent a technical limitation to our study. Color Doppler is considered to be more suitable than conventional pulsed Doppler to delineate and quantify regurgitant areas [14], and may increase the sensitivity for detecting trivial regurgitant jets [18]. It is possible that with color Doppler technique one would find a higher prevalence of physiologic valvular regurgitation in pregnancy.

271

Conclusions Chamber dimensions, annular diameters and prevalence of multivalvular regurgitations increase in a progressive fashion during normal pregnancy, as an expression of a physiologic adaptation process of the heart. Multivalvular regurgitation, trivial or mild, occurs mainly in right-sided valves at the final stages of pregnancy, and must be recognized as a physiologic event probably related to functional annular dilatation. These features have to be considered when evaluating a young pregnant woman with suspected heart disease, in order to avoid misdiagnosing organic valve regurgitation.

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IO

11

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Acknowledgments The authors gratefully acknowledge Dr Uri Elkayam for the critical review of the manuscript, and also Dr Neil F. Novo and Dr Yara Juliano for the statistical assistance. References Elkaiam U, Gleicher, N. Cardiovascular Physiology of Pregnancy. In: Elkaiam and Gleicher, editors. Cardiac problems in pregnancy. Diagnoses and management of maternal and fetal diseases. New York: Alan R. Liss Inc.. 1982; 5-22. Limacher MC, Ware JA, O’Meara ME, Fernandez GC, Young JB. Tricuspid regurgitation during pregnancy: two-dimensional and pulsed Doppler echocardiographic observations. Am J Cardiol 1985; 55: 1059-1062. Campos 0, Martinez EE, Andrade JL et al. Detection of right-sided valve regurgitation during normal pregnancy by Doppler echocardiography [abstract]. J Am Co11 Cardiol 1990; 15: 139A. Sahn D, De.Maria A, Kiss10 J, Weyman AE. The Commitee of M-mode standardization of The American Society of Echo-cardiography. Recommendations regarding quantification in M-mode echocardiographic measurements. Circulation 1978; 58: 1072-1083. Triulzi M, Gillan LD, Gentile F, Newell JB, Weyman AE. Normal adult cross-sectional echocardiographic values: linear dimensions and chambers areas. Echocardiography 1984; 1: 403-426. Akasaka T, Yoshikawa J, Yoshida K et al. Age-related valvular regurgitation: a study by pulsed Doppler echocardiography. Circulation 1987; 76: 262-265. Choong CY, Abascal VM, Weyman J et al. Prevalence of valvular regurgitation by Doppler echocardiography in

13

14

15

16

17

18

19

20

21

22

patients with structurally normal hearts by twodimensional echocardiography. Am Heart J 1989; I 17: 636-642. Berger M. Hecht SR, Van Tosh A, Lingam U. Pulsed and continuous wave Doppler echocardiographic assessment of valvular regurgitation in normal subjects. J Am Coil Cardiol 1989; 13: 1540-1545. Yock PG, Schnittger I, Popp RL. Is continuous wave Doppler too sensitive in diagnosing pathologic valvular regurgitation? [abstract] Circulation 1984; 70 Suppl II: II-381. Yock PG. Naasz C. Schnittger I. Popp RL. Doppler tricuspid and pulmonic regurgitation in normals: is it real? [abstract]. Circulation 1984; 70 Suppl II: 11-157. Tei C, Kisanuki A, Shinisi M et al. Incidence of tricuspid regurgitation in normal subjects according to a new Doppler echocardiographic criterion [Japanese with English abstract]. J Cardiol 1987: 17: 551-558. Kostucki W, Vandenbossche JL. Friart A, Englert M. Pulsed Doppler regurgitant flow patterns of normal valves. Am J Cardiol 1986: 58: 309-313. Takao S, Miyatake K, Izumi S et al. Clinical implications of pulmonary regurgitation in healthy individuals: detection by cross sectional pulsed Doppler echocardiography. Br Heart J 1988; 59: 542-550. Yoshida K, Yoshikawa J, Shakudo M et al. Color Doppler evaluation of valvular regurgitation in normal subjects. Circulation 1988; 78: 840-847. Sahn D, & Maciel BC. Physiological valvular regurgitation Doppler echocardiography and the potential for diatrogenic heart disease. Circulation 1988; 78: 1075-1077. Wittlich N, Erbel R, Drexler M, Mohr-Kahaly S, Brennecke R, Meyer J. Color-Doppler flow mapping of the heart in normal subjects. Echocardiography 1988; 5: 157-171. Nimura Y, Miyatake K, Izumi S. Physiological regurgitation identified by Doppler techniques. Echocardiography 1989; 6: 385-393. Klein A, Burstow DJ, Tajik JA et al. Age-related prevalence of valvular regurgitation in normal subjects: a comprehensive color flow examination of 118 volunteers. J Am Sot Echo 1990; 2: 54-63. Michelsen S, Hurlen M. Otterstad JE. Prevalence of tricuspid and pulmonary regurgitation diagnosed by Doppler in apparently healthy women. Possible influence on their physical performance? Eur Heart J 1988; 9: 61-67. Pollak SJ, McMillan SA. Knopff WD, Wharff R, Yoganathan AP, Felner JM. Cardiac evaluation of women distance runners by echocardiographic color Doppler flow mapping. J Am Co11 Cardiol 1988; 11: 89-93. Douglas PS, Berman GO. O’Toole ML, Hiller WDB, Reichek N. Prevalence of multivalvular regurgitation in athletes. Am J Cardiol 1989; 64: 209-212. Hatle L, Angelsen B. Pulsed and continuous wave Doppler in diagnosis and assessment of various heart lesions. In: Hatle and Angelsen, editors. Doppler ultrasound in

272

23

24

25

cardiology: physical principles and clinical applications. Philadelphia: Lea and Febiger, 1985: 97-282. Rubler S, Damani PM, Pinto ER. Cardiac size and performance during pregnancy estimated with echocardiography. Am J Cardiol 1977; 40: 534-540. Katz R, Karliner JS, Resnik R. Effects of a natural volume overload (pregnancy) on left ventricular performance in normal human subjects. Circulation 1978; 58: 434-441. Robson SC, Hunter S, Boys RJ, Dunlop W. Serial study of factors influencing changes in cardiac output during

26

27

28

1989; 256: human pregnancy. Am J Physiol H1061-H1065. Cahon 0, Banner TE. Doppler estimates of cardiac output during pregnancy. Bull NY Acad Med 1987; 63: 727-73 1 Shalant RC, Silverman ME. Anatomy of The Heart. In: Hurst JW, editor. The heart, arteries and veins. New York: MC Graw-Hill, 1986:16-37. Anderson RH, Becker AE. Cardiac anatomy atlas. London: Churchill Livingstone, 1983; 2. I-5.14.